Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo.
We examined the expression levels of P-glycoprotein (P-Gp)/the human multidrug resistance gene (MDR1) and in vivo chemosensitivity in the 7 osteosarcoma xenografts. Three of seven (43%) osteosarcoma xenografts expressed MDR1 by reverse transcriptase-polymerase chain reaction (RT-PCR). The OSS-516R xenograft selected with vincristine (VCR) from the MDR1-negative xenograft OSS-516, which was sensitive to VCR and doxorubicin (DOX), acquired cross-resistance to DOX. In the OSS-516R, RT-PCR assay showed definite MDR1 expression and immunohistochemical analysis demonstrated P-Gp-positive tumor cells. These results suggest that P-Gp/MDR1 overexpression is related to multidrug resistance in human osteosarcoma in vivo.
Suto
R
R
Department of Orthopedics, Tokai University, School of Medicine, Bohseidai, Isehara-shi, Kanagawa 259-11, Japan.
Abe
Y
Y
Nakamura
M
M
Ohnishi
Y
Y
Yoshimura
M
M
Lee
Y H
YH
Imanishi
T
T
Yamazaki
H
H
Kijima
H
H
Tokunaga
T
T
Oshika
Y
Y
Hiraoka
N
N
Tamaoki
N
N
Fukuda
H
H
Ueyama
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014750:Vincristine / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014750:Vincristine; D004317:Doxorubicin